Fig. 2: CDK9 is a vulnerability in MCL-1 independent T-cell lymphomas.

A BH3 profiling was performed using a MCL-1 selective only BH3 peptide (MS1; 5, 10 μM) in T-cell lymphoma cell lines. Cell lines with loss of cytochrome c, measured by percentage (%) of depolarization, in the presence of MS1, indicating MCL-1 dependence, are highlighted in red. MCL-1 dependent cell lines were identified if their percentage of depolarization exceed 10% or if they exhibit higher depolarization in higher concentration of MS1 peptide. B, C Cell viability was determined in a panel of cell lines treated with a MCL-1 selective inhibitor (S63845). MCL-1 dependent and independent cells are indicated in red and blue, respectively. Cell viability at 600 nM is summarized in (C) stratified by MCL-1 dependence. D Cell viability was determined in MCL-1 dependent cell lines treated with AZD4573 (2-fold serial dilution from 200 nM for 24 h). E Apoptosis was measured by cleaved PARP and Caspase-3 IB in representative MCL-1 dependent (MAC1, SUP-M2 and DEL) cells. F Cell viability was determined in MCL-1 independent cell lines, SS specimens and normal T cells (HD) from healthy donors (n = 3) treated with AZD4573 (2-fold serial dilution from 200 nM for 24 h). G Apoptosis was measured by cleaved PARP and Caspase-3 IB in representative MCL-1 independent (H9, MyLa CD4, SUP-T1) cells. H Cell viability was determined in MCL-1 dependent (in red) and independent (in blue) cell lines, treated with selective CDK9 inhibitor Enitociclib (2-fold serial dilution from 400 nM for 24 h). I IC50 of AZD4573 is shown in each cell line stratified by MCL-1 dependency. Data are represented as mean ± SEM and were analyzed using Welch’s unpaired t-test. **p < 0.01.